ObjectiveTo investigate the influencing factors and independent risk factors for lower extremity deep vein thrombosis （DVT） in patients with acute necrotizing pancreatitis （ANP）， to analyze the effectiveness of three commonly used risk assessment models for thrombosis （Caprini score， Padua score， and Wells score）， and to provide a reference for clinical identification of high-risk individuals and optimization of prevention and treatment strategies. MethodsA retrospective analysis was performed for the clinical data of 320 patients with ANP who were admitted to Luzhou People’s Hospital and The Affiliated Hospital of Southwest Medical University from April 2013 to April 2024， and according to the presence or absence of DVT during hospitalization， the patients were divided into thrombosis group with 25 patients and control group with 295 patients. After propensity score matching， the two groups were compared in terms of past history and various examination results during hospitalization. The risk factors for lower extremity DVT in ANP patients during hospitalization were analyzed through univariate and multivariate Logistic regression， and a DVT risk prediction model was established based on independent influencing factors. The receiver operating characteristic （ROC） curve was used to assess the performance of models， and the DeLong test was used for comparison of the area under the ROC curve （AUC）， sensitivity， and specificity. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. ResultsAfter matching， the patients were divided into thrombosis group with 24 patients and control group with 112 patients. The clinical characteristics analysis showed that compared with the control group， the thrombosis group had significantly higher degree of pancreatic necrosis， D-dimer level， Bedside Index for Severity in Acute Pancreatitis （BISAP） score， and proportion of patients undergoing dialysis （all P<0.05）. The multivariable Logistic regression analysis showed that BISAP score， degree of pancreatic necrosis， and D-dimer level were independent risk factors for lower extremity DVT in ANP patients during hospitalization （all P<0.05）. The BISAP-Caprini score model had an AUC of 0.832 （95% confidence interval： 0.722 — 0.942， P<0.001） in predicting the risk of lower extremity DVT， with a Youden index of 1.661， an optimal cut-off value of 0.26， a sensitivity of 75.0%， and a specificity of 91.1%. ConclusionD-dimer， BISAP score， and the degree of pancreatic necrosis are independent risk factors for lower extremity DVT in patients with ANP during hospitalization， and the BISAP-Caprini score model can effectively predict the risk of DVT in ANP patients.

BACKGROUND:Rheumatoid arthritis is a complex autoimmune disease characterized by joint swelling,pain,and progressive damage.The basic pathological changes include synovitis and pannus formation,with T lymphocyte infiltration being the key to its pathogenesis.In recent years,the application of traditional Chinese medicine(TCM)monomers in the treatment of rheumatoid arthritis has attracted increasing attention.They have shown long-lasting effcacy and fewer side effects by regulating the T helper cell 17(Th17)/regulatory T cells(Treg)balance in the treatment of rheumatoid arthritis.OBJECTIVE:To discuss the mechanisms by which TCM monomers regulate the Th17/Treg balance to treat rheumatoid arthritis,based on the latest basic research,providing a solid theoretical basis for future applications of TCM in the treatment of rheumatoid arthritis.METHODS:Using keywords such as"rheumatoid arthritis,Th17/Treg,traditional Chinese medicine,Chinese herbal monomer,"and their Chinese equivalents,literature searches were conducted in PubMed,Web of Science,Embase,Cochrane,VIP,CBM,CNKI,and WanFang databases for relevant studies from their inception to August 2024.Inclusion and exclusion criteria were established,and the articles were screened by reading the titles,abstracts,and full texts.Finally,57 relevant articles were included.RESULTS AND CONCLUSION:(1)TCM monomers have immunoregulatory effects in the treatment of rheumatoid arthritis.They exert therapeutic effects by maintaining the Th17/Treg balance through the regulation of transcription factors,cytokines,signaling pathways,and miRNAs.(2)There may be synergistic effects among some TCM monomers,but the specific mechanisms and enhancement effects in regulating the Th17/Treg balance require further exploration.(3)Regulating the Th17/Treg balance using TCM monomers may become a key clinical therapy for the treatment of rheumatoid arthritis.

Paclitaxel(PTX)is a first-line chemotherapy drug for breast cancer,but its resistance issues significantly impact clinical treatment efficacy.Fucosylation,especially core fucosylation,is closely related to tumor chemoresistance,resulting in poor chemotherapy responses and poor prognosis in patients.In this study,we investigated the effect and mechanism of the fucosylation inhibitor 2-fluorofucose(2-F-Fuc)on the chemosensitivity of paclitaxel-resistant breast cancer MCF-7/PTX cells.The drug resistanceindex(RI)of MCF-7/PTX cells was 8.49 by MTT assays.Western blotting,real-time PCR,enzyme-linked immu-nosorbent assay(ELISA)and Lens Culinaris Agglutinin(LCA)lectin imprinting showed that compared with MCF-7 cells,the expression of FUT8,MDR1and core fucosylation in MCF-7/PTX cells was high.Western blotting showed that 2-F-Fuc had a significant inhibitory effect on the growth of MCF-7/PTX cells,and the expression levels of FUT8 and MDR1 were significantly down-regulated after 2-F-Fuc treatment,and the down-regulation was more pronounced in the PTX and 2-F-Fuc combination group(P＜0.05).Compared to the control,expression of PCNA in MCF-7/PTX cells in the PTX and the 2-F-Fuc group were down-regulated,and the apoptosis-related proteins,such as cleaved caspase-3 and Bax/Bcl-2 were in-creased.The level of p-PI3K and p-AKT were down-regulated,and the changes in the combination of 2-F-Fuc and PTX were more robust(P＜0.05).The above results showed that the core fucosylation level of MCF-7/PTX cells was significantly increased,and 2-F-Fuc could reduce the core fucosylation level of MCF-7/PTX cells by inhibiting the expression of FUT8,and enhance the sensitivity of drug-resistant cells to PTX,which may correlate with the downregulation of PI3K/AKT signaling pathway proteins.

OBJECTIVE To explore the diagnostic value of combined detection of microRNA(miRNA)and alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)in ascites and serum ex-tracellular vesicles(EVs)for hepatitis B virus(HBV)-related primary hepatocellular carcinoma(HCC).METHODS From Nov.2023 to Nov.2024,41 patients with liver cancer and 26 patients with liver cirrhosis who underwent ascites placement or ascites concentration and reinfusion procedures at the Fifth Medical Center of Chi-nese PLA General Hospital were selected as study subjects.Ascites and serum samples were collected.Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-21,miR-125a,miR-150 and miR-200a in EVs.Chemiluminescence was used to measure the levels of AFP and PIVKA-Ⅱ in ascites,serum and EVs from ascites and serum.An artificial neural network was utilized to con-struct a combined diagnostic model of serum and ascites markers.RESULTS The area under the curve(AUC)for distinguishing HCC from liver cirrhosis using a combination of serum and other indicators was 0.933.The AUC for distinguishing HCC from liver cirrhosis using a combination of ascites and other indicators was 0.912.By screening all detected indicators using an artificial neural network and incorporating indicators with a relative im-portance＞0.5 into the diagnostic model,the model included four indicators:ascites AFP,ascites EVs miR-21,ascites EVs miR-200a and serum EVs miR-200a.This model had a sensitivity of 80.77％,a specificity of 87.80％and an AUC of 0.960 for distinguishing HCC from liver cirrhosis patients.CONCLUSION The combined diagnos-tic markers of miRNA,AFP and PIVKA-Ⅱ in ascites and serum-derived EVs have good application value in the diagnosis of HCC.

Objective To explore the role of Schlafen4(SLFN4)in acute pneumonia induced by hypervirulent Klebsiella pneumoniae(hvKp)via intratracheal aerosolization.Methods Differential expression gene Slfn4 was identified after infection with hvKp based on RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)data before Slfn4-/-mice were obtained via CRISPR/Cas gene editing technology.Slfn4-/-mice and wild mice were challenged via intratracheal aerosolization.Mortality and weight changes were recorded for 14 d,while pathological changes and expression levels of interleukin-6(IL-6),IL-17A,IL-1β,and tumor necrosis factor-α(TNF-α)were detected at 48 h post-infection.Results SLFN4 expression was significantly increased in wild mice after infection with hvKp.Survival was significantly increased,and weight loss was mitigated before gradual recovery in Slfn4-/-mice after infection.The knockout of SLFN4 attenuated alveolar wall thickening,diminished neutrophil infiltration,and suppressed pro-inflammatory cytokine production(IL-6,IL-17A,IL-1β,TNF-α)in the lung at 48 h post-infection.Conclusion The deletion of SLFN4 may suppress the expression of specific pro-inflammatory cytokines and attenuate neutrophil over-recruitment in the lung,thereby alleviating pneumonia in mice after hvKp infection.

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.